tbuckley/cabot-search huggingface dataset:
Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development
Authors: Xiaoyue Liang, Ding Chen, Jiannan Wang, Binyou Liao, Jiawei Shen, Xingchen Ye, Zheng Wang, Chengguang Zhu, Lichen Gou, Xinxuan Zhou, Lei Cheng, Biao Ren, Xuedong Zhou
Journal: International Journal of Oral Science (2023)

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Signaling pathways in macrophages: molecular mechanisms and therapeutic targets
Authors: Ming Li, Mengjie Wang, Yuanjia Wen, Hongfei Zhang, Guang‐Nian Zhao, Qinglei Gao
Journal: MedComm (2023)

Abstract Macrophages play diverse roles in development, homeostasis, and immunity. Accordingly, the dysfunction of macrophages is involved in the occurrence and progression of various diseases, such as coronavirus disease 2019 and atherosclerosis. The protective or pathogenic effect that macrophages exert in different conditions largely depends on their functional plasticity, which is regulated via signal transduction such as Janus kinase–signal transducer and activator of transcription, Wnt and Notch pathways, stimulated by environmental cues. Over the past few decades, the molecular mechanisms of signaling pathways in macrophages have been gradually elucidated, providing more alternative therapeutic targets for diseases treatment. Here, we provide an overview of the basic physiology of macrophages and expound the regulatory pathways within them. We also address the crucial role macrophages play in the pathogenesis of diseases, including autoimmune, neurodegenerative, metabolic, infectious diseases, and cancer, with a focus on advances in macrophage‐targeted strategies exploring modulation of components and regulators of signaling pathways. Last, we discuss the challenges and possible solutions of macrophage‐targeted therapy in clinical applications. We hope that this comprehensive review will provide directions for further research on therapeutic strategies targeting macrophage signaling pathways, which are promising to improve the efficacy of disease treatment.
Global health burden and cost of lead exposure in children and adults: a health impact and economic modelling analysis
Authors: Bjorn Larsen, Ernesto Sánchez-Triana
Journal: The Lancet Planetary Health (2023)

Lead exposure is a worldwide health risk despite substantial declines in blood lead levels following the leaded gasoline phase-out. For the first time, to our knowledge, we aimed to estimate the global burden and cost of intelligence quotient (IQ) loss and cardiovascular disease mortality from lead exposure.In this modelling study, we used country blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We estimated IQ loss (presented as estimated loss in IQ points with 95% CIs) in the global population of children younger than 5 years using the blood lead level-IQ loss function from an international pooled analysis. We estimated the cost of IQ loss, which was calculated only for the proportion of children expected to enter the labour force, as the present value of loss in lifetime income from the IQ loss (presented as cost in US dollars and percentage of gross domestic product with a range). We estimated cardiovascular deaths (with 95% CIs) due to lead exposure among people aged 25 years or older using a health impact model that captures the effect of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension. Finally, we used values of statistical life to estimate the welfare cost of premature mortality (presented as cost in US dollars and percentage of GDP). All estimates were calculated by World Bank income classification and region (for low-income and middle-income countries [LMICs] only) for 2019.We estimated that children younger than 5 years lost 765 million (95% CI 443-1098) IQ points and that 5 545 000 (2 305 000-8 271 000) adults died from cardiovascular disease in 2019 due to lead exposure. 729 million of the IQ points lost (95·3% of the total global IQ loss) and 5 004 000 (90·2% of total) cardiovascular disease deaths due to lead exposure occurred in LMICs. IQ loss in LMICs was nearly 80% higher than a previous estimate. Cardiovascular disease deaths were six times higher than the GBD 2019 estimate. The global cost of lead exposure was US$6·0 trillion (range 2·6-9·0) in 2019, which was equivalent to 6·9% (3·1-10·4) of the global gross domestic product. 77% (range 70-78) of the cost was the welfare cost of cardiovascular disease mortality, and 23% (22-30) was the present value of future income losses from IQ loss.Our findings suggest that global lead exposure has health and economic costs at par with PM2·5 air pollution. However, much work remains to improve the quality of blood lead level measurement data, especially in LMICs.The Korea Green Growth Trust Fund and the World Bank's Pollution Management and Environmental Health Program.
International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy
Authors: Sanja Dacic, William Travis, Mary Redman, Anjali Saqi, Wendy A. Cooper, Alain Borczuk, Jin-Haeng Chung, Carolyn Glass, Javier Martin Lopez, Anja C. Roden, Lynette Sholl, Annikka Weissferdt, Juan Posadas, Angela Walker, Hu Zhu, Manuja T. Wijeratne, Casey Connolly, Murry Wynes, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, J.Jack Lee, Sabina Berezowska, Teh-Ying Chou, Keith Kerr, Andrew Nicholson, Claudia Poleri, Kurt A. Schalper, Ming-Sound Tsao, David P. Carbone, Neal Ready, Tina Cascone, John Heymach, Boris Sepesi, Catherine Shu, Naiyer Rizvi, Josuha Sonett, Nasser Altorki, Mariano Provencio, Paul A. Bunn, Mark G. Kris, Chandra P. Belani, Karen Kelly, Ignacio Wistuba
Journal: Journal of Thoracic Oncology (2023)
Deficiency of salt‐inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes
Authors: Jiaojiao Zhu, Chao Li, Ping Wang, Yuhao Liu, Zhongqiu Li, Zhongmin Chen, Ying Zhang, Bin Wang, Xueping Li, Ziyan Yan, Xinxin Liang, Shenghui Zhou, Xingkun Ao, Maoxiang Zhu, Pingkun Zhou, Yongqing Gu
Journal: MedComm (2023)

Salt-inducible kinase 2 (SIK2) belongs to the serine/threonine protein kinases of the AMPK/SNF1 family, which has important roles in cell cycle, tumor, melanogenesis, neuronal damage repair and apoptosis. Recent studies showed that SIK2 regulates the macrophage polarization to make a balance between inflammation and macrophage. Macrophage is critical to initiate immune regulation, however, whether SIK2 can be involved in immune regulation is not still well understood. Here, we revealed that the protein of SIK2 was highly expressed in thymus, spleen, lung, and brain. And SIK2 protein content increased in RAW264.7 and AHH1 cells with a time and dose-dependent after-ionizing radiation (IR). Inhibition of SIK2 could promote AHH1 cells apoptosis Moreover, we used the Cre-LoxP system to construct the SIK2+/- mice, and the research on function suggested that the deficiency of SIK2 could promote the sensitivity of IR. The deficiency of SIK2 promoted the immune injury via inhibiting the maturation of T cells and B cells. Furthermore, the TCRβ rearrangement was inhibited by the deficiency of SIK2. Collectively, this study demonstrated that SIK2 provides an essential function of regulating immune injury, which will provide new ideas for the treatment of immune injury-related diseases.
Leveraging Coupling Effect‐Enhanced Surface Plasmon Resonance of Ruthenium Nanocrystal‐Decorated Mesoporous Silica Nanoparticles for Boosted Photothermal Immunotherapy
Authors: Pin Li, Zheng Chen, Fan Xia, Nan Wang, Jing Zhao, Xi Hu, Mingjian Zhu, Shiyi Yu, Daishun Ling, Fangyuan Li
Journal: Advanced Healthcare Materials (2023)

Photothermal immunotherapy (PTI) has emerged as a promising approach for cancer treatment, while its efficacy is often hindered by the immunosuppressive tumor microenvironment (TME). Here, this work presents a multifunctional platform for tumor PTI based on ruthenium nanocrystal-decorated mesoporous silica nanoparticles (RuNC-MSN). By precisely regulating the distance between RuNC on MSN, this work achieves a remarkable enhancement in surface plasmon resonance of RuNC, leading to a significant improvement in the photothermal efficiency of RuNC-MSN. Furthermore, the inherent catalase-like activity of RuNC-MSN enables effective modulation of the immunosuppressive TME, thereby facilitating an enhanced immune response triggered by the photothermal effect-mediated immunogenic cell death (ICD). As a result, RuNC-MSN exhibits superior PTI performance, resulting in pronounced inhibition of primary tumor and metastasis. This study highlights the rational design of PTI agents with coupling effect-enhanced surface plasmon resonance, enabling simultaneous induction of ICD and regulation of the immunosuppressive TME, thereby significantly boosting PTI efficacy.
Neutral sphingomyelinase blockade enhances hematopoietic stem cell fitness through an integrated stress response
Authors: Stephanie N. Hurwitz, Seul K. Jung, Danielle R. Kobulsky, Hossein Fazelinia, Lynn A. Spruce, Empar Baltasar Pérez, Nathalie Groen, Clementina Mesaros, Peter Kurre
Journal: Blood (2023)
Endoscopic resection of large anastomotic polyps is safe and effective
Authors: Oliver Cronin, Sunil Gupta, Julia Gauci, Anthony Whitfield, Timothy O'Sullivan, Muhammad Abuarisha, Hunter Wang, Eric Yong Tat Lee, Stephen J Williams, Nicholas Graeme Burgess, Michael J. Bourke
Journal: Endoscopy (2023)

Abstract Background Large (≥20mm) adenomatous anastomotic polyps (LAAPs) are uncommon. Data pertaining to their prevalence, characteristics, and the efficacy of endoscopic resection (ER) are absent. A safe and effective strategy for ER would reduce morbidity and healthcare costs. Methods Large nonpedunculated colorectal polyps of ≥20mm (LNPCPs) referred for ER were prospectively studied. Multiple data points were recorded including anastomotic location, polyp morphology, resection modality, complications, and technical success. Results Over 7 years until November 2022, 2629 lesions were referred. Of these, 10 (0.4%) were LAAPs (median size 35 mm [interquartile range (IQR) 30–40mm]). All LAAPs were removed by piecemeal endoscopic mucosal resection (EMR), most (n=9; 90%) in combination with cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST). On comparison of the LAAP group with the conventional LNPCP group, CAST was more commonly used (90% vs. 9%; P&lt;0.001) and deep mural injury (DMI) type II was more frequent (40% vs. 11%, P=0.003); however, significant DMI (III–V) did not occur. At 6 month (IQR 5.25–6 months) surveillance, there was no recurrence in any of the 10 cases. There were no serious adverse events. Conclusions LAAPs present unique challenges owing to their location overlying an anastomosis. Despite these challenges they can be safely and effectively managed endoscopically without recurrence at endoscopic follow-up.
Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial
Authors: Bhumsuk Keam, Min Hee Hong, Seong Hoon Shin, Seong Gu Heo, Ji Eun Kim, Hee Kyung Ahn, Yun-Gyoo Lee, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Sung-Bae Kim, Sang-Cheol Lee, Min Kyoung Kim, Sang Hee Cho, So Yeon Oh, Sang-Gon Park, Shinwon Hwang, Byung-Ho Nam, Sangwoo Kim, Hye Ryun Kim, Hwan Jung Yun
Journal: Journal of Clinical Oncology (2023)

PURPOSE A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC. METHODS In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti–PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment. RESULTS Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths. CONCLUSION To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.
Corrigendum to “How to: EUCAST recommendations on the screening procedure E.Def 10.1 for the detection of azole resistance in Aspergillus fumigatus isolates using four-well azole-containing agar plates” [Clin Microbiol Infect 25 (2019) 681-687]
Authors: J. Guinea, P.E. Verweij, J. Meletiadis, J.W. Mouton, F. Barchiesi, M.C. Arendrup
Journal: Clinical Microbiology and Infection (2023)
Early Endophthalmitis Incidence and Risk Factors after Glaucoma Surgery in the Medicare Population from 2016 to 2019
Authors: Jasdeep Sabharwal, Xi Dai, Chen Dun, Ariel Chen, Muhammad Ali, Oliver D. Schein, Pradeep Y. Ramulu, Martin Makary, Thomas V. Johnson, Fasika Woreta
Journal: Ophthalmology (2023)
Flexible Allyl‐Modified Gelatin Photoclick Resin Tailored for Volumetric Bioprinting of Matrices for Soft Tissue Engineering
Authors: Alessandro Cianciosi, Sabrina Stecher, Maxi Löffler, Petra Bauer‐Kreisel, Khoon S. Lim, Tim B. F. Woodfield, Jürgen Groll, Torsten Blunk, Tomasz Jungst
Journal: Advanced Healthcare Materials (2023)

Volumetric bioprinting (VBP) is a light-based 3D printing platform, which recently prompted a paradigm shift for additive manufacturing (AM) techniques considering its capability to enable the fabrication of complex cell-laden geometries in tens of seconds with high spatiotemporal control and pattern accuracy. A flexible allyl-modified gelatin (gelAGE)-based photoclick resin is developed in this study to fabricate matrices with exceptionally soft polymer networks (0.2-1.0 kPa). The gelAGE-based resin formulations are designed to exploit the fast thiol-ene crosslinking in combination with a four-arm thiolated polyethylene glycol (PEG4SH) in the presence of a photoinitiator. The flexibility of the gelAGE biomaterial platform allows one to tailor its concentration spanning from 2.75% to 6% and to vary the allyl to thiol ratio without hampering the photocrosslinking efficiency. The thiol-ene crosslinking enables the production of viable cell-material constructs with a high throughput in tens of seconds. The suitability of the gelAGE-based resins is demonstrated by adipogenic differentiation of adipose-derived stromal cells (ASC) after VBP and by the printing of more fragile adipocytes as a proof-of-concept. Taken together, this study introduces a soft photoclick resin which paves the way for volumetric printing applications toward soft tissue engineering.
Spatial transcriptomics reveals distinct tissue niches linked with steroid responsiveness in acute gastrointestinal GVHD
Authors: Bidish K. Patel, Michael J. Raabe, Evan R. Lang, Yuhui Song, Chenyue Lu, Vikram Deshpande, Linda T. Nieman, Martin J. Aryee, Yi-Bin Chen, David T. Ting, Zachariah DeFilipp
Journal: Blood (2023)
Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment
Authors: Roberta Sanfilippo, Marta Sbaraglia, Chiara Fabbroni, Sabrina Croce, Isabelle Ray-Coquard, Fatma Guermazi, Biagio Paolini, Félix Blanc-Durand, Axel Lecesne, Valentina Chiappa, Angelo Paolo Dei Tos, Paolo Giovanni Casali
Journal: Clinical Cancer Research (2023)

Abstract Purpose: According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS. In recent years, some sarcoma centers valued the less aggressive clinical behavior of several recurring STUMP and, given their expression of estrogen and progesterone receptors, started to treat them with hormonal therapy. Experimental Design: This was a retrospective cohort analysis conducted at three referral centers joining the Leiomyosarcoma Foundation Roundtable. We selected all cases of uterine smooth muscle tumors consistent with STUMP and treated with hormonal therapy. Results: 27 consecutive patients were identified. Median age at diagnosis was 43 years. Stage was IA-IB in more than 70% of patients. In these patients, median time to relapse was 62 months. Sites of first relapses were mostly pelvis and peritoneum (76%). After a median follow-up of 49 months, 14 patients (52%) had a partial response while 10 (37%) had a minor response or stable disease. Median time to progression was not reached. Conclusions: We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. On the basis of these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a “low-grade ULMS.”
Relationship between Unstable Housing, Food Insecurity, and Vision Status in the MI-SIGHT Community Eye Disease Screening Program
Authors: Mikaelah A. Johnson-Griggs, Patrice M. Hicks, Ming-Chen Lu, Eric Sherman, Leslie M. Niziol, Angela R. Elam, Maria A. Woodward, Amanda K. Bicket, Olivia J. Killeen, Sarah Wood, Denise John, Leroy Johnson, Martha Kershaw, David C. Musch, Paula Anne Newman-Casey
Journal: Ophthalmology (2023)
Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes
Authors: Jasaman Tojjar, Matti Cervin, Emma Hedlund, Qefsere Brahimi, Gun Forsander, Helena Elding Larsson, Johnny Ludvigsson, Ulf Samuelsson, Claude Marcus, Martina Persson, Annelie Carlsson
Journal: Diabetes Care (2023)

OBJECTIVE To examine sex differences in children with newly diagnosed type 1 diabetes (T1D) with respect to age at diagnosis, presence of autoantibodies (GAD antibody [GADA], insulinoma-associated protein 2 [IA-2A], insulin autoantibody [IAA], and zinc transporter 8 autoantibody), and HLA risk. RESEARCH DESIGN AND METHODS A population-based nationwide sample of 3,645 Swedish children at T1D diagnosis was used. RESULTS Girls were younger at T1D diagnosis (9.53 vs. 10.23 years; P &amp;lt; 0.001), more likely to be autoantibody-positive (94.7% vs. 92.0%; P = 0.002), more often positive for multiple autoantibodies (P &amp;lt; 0.001), more likely to be positive for GADA (64.9% vs. 49.0%; P &amp;lt; 0.001), and less likely to be positive for IAA (32.3% vs. 33.8%; P = 0.016). Small sex differences in HLA risk were found in children &amp;lt;9 years of age. CONCLUSIONS The disease mechanisms leading to T1D may influence the immune system differently in girls and boys.
Reply to: Tacrolimus and the Treatment of Pulmonary Fibrosis
Authors: Toyoshi Yanagihara, Kazuya Tsubouchi, Martin R. J. Kolb
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: Tacrolimus and the Treatment of Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Use of big data and machine learning algorithms to extract possible treatment targets in neurodevelopmental disorders
Authors: Muhammad Ammar Malik, Stephen V. Faraone, Tom Michoel, Jan Haavik
Journal: Pharmacology & Therapeutics (2023)

Neurodevelopmental disorders (NDDs) impact multiple aspects of an individual's functioning, including social interactions, communication, and behaviors. The underlying biological mechanisms of NDDs are not yet fully understood, and pharmacological treatments have been limited in their effectiveness, in part due to the complex nature of these disorders and the heterogeneity of symptoms across individuals. Identifying genetic loci associated with NDDs can help in understanding biological mechanisms and potentially lead to the development of new treatments. However, the polygenic nature of these complex disorders has made identifying new treatment targets from genome-wide association studies (GWAS) challenging. Recent advances in the fields of big data and high-throughput tools have provided radically new insights into the underlying biological mechanism of NDDs. This paper reviews various big data approaches, including classical and more recent techniques like deep learning, which can identify potential treatment targets from GWAS and other omics data, with a particular emphasis on NDDs. We also emphasize the increasing importance of explainable and causal machine learning (ML) methods that can aid in identifying genes, molecular pathways, and more complex biological processes that may be future targets of intervention in these disorders. We conclude that these new developments in genetics and ML hold promise for advancing our understanding of NDDs and identifying novel treatment targets.